The long-term objectives of these studies are to develop virus-based HIV vaccine vectors for which there is no pre-existing immunity in humans and to test these in non-human primate models of SIV/AIDS. The vectors being studied are based on recombinant vesicular stomatitis virus (VSV) and Semliki Forest Virus (SFV-G) replicon particles that propagate through expression of the VSV G protein. When used in a heterologous prime-boost regimen these vectors expressing SIV Env and Gag proteins provided significant and apparently sterilizing immunity to high-dose mucosal challenge with an SIV quasispecies. The major objective of the proposed continuing studies is to determine the immune correlates of protection conferred by the vaccine. The major hypothesis to be tested is that mucosal antibody to Env is involved in conferring the immunity. As part of this study, founder virus envelope sequences from infected control animals will be determined and neutralizing antibody assays for these envelopes will be developed. These assays will then be used to determine if mucosal antibody levels correlate with protection from challenge. The durability of the vaccine protection will be determined as well as the ability to protect from heterologous challenge with cloned viruses. The proposed studies will also determine which SIV gene(s) are required for protection. Non-human primate models of SIV/AIDS are the most relevant models currently available for HIV vaccine studies. These continuing studies are relevant to guiding approaches to development of an effective HIV vaccine.